1. Field of the Invention
The present invention relates generally to a blood testing tool used for a blood test.
2. Related Background Art
In a blood test, a sheet blood testing tool consumed per specimen is used for various purposes. Examples of this testing tool include those that retain blood, from which blood to be tested is extracted; and those that are pre-impregnated with a reagent or the like so that the blood and the reagent react with each other with the result being measured by an optical or electrochemical method, etc.
Such a blood testing tool has been used for various purposes in general clinical tests or the like. In addition, the suitability of such a blood testing tool has been studied for use in remote clinical testing systems. Indeed it is actually used in certain remote clinical testing systems. In such a remote clinical testing system, a patient collects blood by himself at home, and the blood testing tool is impregnated with the blood. This is then dried, and the blood testing tool is then mailed to a test institute such as a hospital for testing. The patient who mailed the blood can then be informed of the test result by a mail or by visiting the hospital.
When the test item is a component of blood plasma or blood serum such as blood glucose or the like, blood cells must be separated in the blood testing tool. Generally, in a conventional blood testing tool, a blood cell separator such as a glass filter or the like is incorporated into the blood testing tool. However, a blood testing tool having an asymmetric porous membrane with pores whose sizes vary in a thickness direction has been developed recently. When blood is supplied to the porous membrane from the side having larger pores, blood cells are separated. The blood penetrates in the thickness direction and thus blood plasma or blood serum comes out of the other side. An advantage of using a blood testing tool having a porous membrane is that the clogging of blood cells can be prevented.
However, such conventional blood testing tools have the disadvantage that only a small amount of blood plasma or blood serum can be collected. For instance, a collection rate of blood plasma or blood serum in conventional blood testing tools is about 25% at most. Therefore, when a trace component in the blood plasma or blood serum is to be analyzed, there is the possibility that the trace component cannot be analyzed correctly due to the small size of the sample obtained. Particularly, in the case of the remote clinical testing system, where a patient collects blood himself, there is the difficulty of obtaining a large enough blood sample. In addition, since there are many test items, an increased amount of blood plasma or blood serum must be collected.
The present invention at least in its preferred embodiments is intended to provide a blood testing tool that can separate blood cells easily and can collect blood plasma or blood serum with a high yield.
In order to achieve the above-mentioned object, a blood testing tool includes an asymmetric porous membrane with a pore size distribution in which an average pore size varies so that it is reduced continuously or discontinuously in a thickness direction, wherein the asymmetric porous membrane includes a blood supply portion, a development portion, and a blood-cell blocking portion formed between the blood supply portion and the development portion, pores in the blood-cell blocking portion include only pores through which blood cells cannot pass, the arrangement being such that when blood is supplied to the blood supply portion at a side having larger pores, the blood moves in a direction substantially parallel to a surface of the asymmetric porous membrane by capillary action, but only blood plasma or blood serum moves into the development portion.
As described above, the blood testing tool of the present invention allows blood to move in the porous membrane in the direction parallel to the surface (a transverse direction) and blood cells can be separated during the movement. This is different from the conventional case where blood moves in a thickness direction and can induce a strong capillary action. Thus a large amount of blood plasma or blood serum can be collected. In addition, a sufficient region for retaining blood plasma or blood serum reaching the region can be secured. According to the preferred form of the blood testing tool of the present invention, therefore, blood plasma or blood serum can be obtained with an excellent collection rate and blood cells also can be separated adequately. In the blood testing tool, the collection rate of blood plasma or blood serum may be, for example, about 60 to 70%. In the blood testing tool, since the blood supply portion and the development portion do not lie one on top of another, measurement can be carried out from any sides of the development portion, when the measurement is to be carried out directly with respect to the blood testing tool by an optical method (including visual observation). In the present invention, the xe2x80x9cpores through which blood cells cannot passxe2x80x9d are not limited to the pores with smaller sizes than spherical diameters of blood cells, but may be pores through which blood cells eventually cannot pass regardless of the mechanism of preventing blood cells from passing through the pores. Therefore, the pores through which blood cells cannot pass may include pores larger than the spherical diameters of blood cells. In addition, the xe2x80x9caverage pore size varies so that it is reduced discontinuouslyxe2x80x9d means that the average pore size may vary, for example, to be reduced in a stepwise manner.
Preferably, the blood testing tool further includes a groove formed between the blood supply portion and the development portion, wherein a portion between a bottom of the groove and a part of a surface of the asymmetric porous membrane corresponding to the bottom is the blood-cell blocking portion.
The groove may be formed by compression or cutting out of a part of the asymmetric porous membrane.
Preferably, pores in the development portion include only pores through which blood cells cannot pass. In this case, the development portion also may function as the blood-cell blocking portion.
Preferably, the pores in the blood-cell blocking portion have a pore size in a range of 1 to 50 xcexcm, more preferably 5 to 30 xcexcm, and particularly preferably 10 to 20 xcexcm.
It also is preferable that in the asymmetric porous membrane, the maximum pore size is in a range of 30 to 300 xcexcm and the minimum pore size is in a range of 1 to 30 xcexcm.
Preferably, the asymmetric porous membrane has a single layer structure. The single layer structure preferably includes no interface (i.e. no contact surface between layers). Therefore, blood plasma or blood serum can move more easily than if an interface were present, and hemolysis or the like caused by contact between blood cells and an interface can be prevented.
Preferably, the asymmetric porous membrane is supported by a supporter. Accordingly, regardless of the strength of the porous membrane, a blood testing tool with a sufficient strength can be obtained, which enables easy handling.
Preferably, the asymmetric porous membrane is formed from at least one resin selected from polysulfone, polyamide, polyimide, polycarbonate, polystyrene, polyaryl hydrazide, and the like. More preferably, the porous membrane is formed of polysulfone.
Furthermore, it is preferable that the asymmetric porous membrane is treated to be provided with hydrophilicity. This allows blood to develop easily in the porous membrane.
Preferably, the development portion contains a stabilizing agent for maintaining stability of components in the blood plasma or the blood serum.
Preferably, the development portion contains an analytical reagent. Accordingly, blood plasma or blood serum separated in the blood testing tool is allowed to react with the analytical reagent without being collected from the blood testing tool, thus analysis may be conducted.
The blood testing tool of the present invention may further include a holder, and the porous membrane may be contained in the holder. Examples of such a blood testing tool (hereinafter, referred to as a xe2x80x9ccontained-type blood testing toolxe2x80x9d) include, for instance, the following two forms.
In one such example there is a contained-type blood testing tool as discussed above further including a holder, wherein the holder contains the asymmetric porous membrane and a space with a size preventing a capillary phenomenon from occurring is formed between an inner wall of the holder and a portion between the development portion and the blood supply portion.
In a conventional blood testing tool with an asymmetric porous membrane contained in a holder, blood might penetrate not into the porous membrane but between the porous membrane and the inner wall of the holder in some cases. The blood thus penetrated is not separated by a chromatography effect. Therefore, blood components separated inside the porous membrane may be contaminated with the unseparated blood that has penetrated as described above, which may affect analysis. As a means for solving this problem, consideration can be given to a method of providing a sufficiently large development portion in the porous membrane. However, this makes the blood testing tool too big and costly, and inconvenient to use. Considering this, the present inventors studied the blood penetration between the porous membrane and the inner wall of the holder and found that it was caused by a capillary phenomenon occurring between the inner wall of the holder and the porous membrane. In the example of a contained-type blood testing tool in the present invention, therefore, blood cells can be separated adequately and an excellent collection rate can be achieved as described above. In addition, a space with a size not allowing this capillary phenomenon to occur is provided between the inner wall and the portion (hereinafter, also referred to as a xe2x80x9cboundary portionxe2x80x9d) between the development portion and the blood supply portion of the porous membrane, thus preventing unseparated blood from penetrating therebetween.
In the porous membrane contained in the contained-type blood testing tool, with respect to the flow of blood inside the porous membrane, the blood supply portion denotes a part or the whole part of the portion upstream from the boundary portion, and the development portion denotes a part or the whole part of the portion downstream from the boundary portion.
Preferably, the portion between the blood supply portion and the development portion is the blood-cell blocking portion.
Preferably, a protruding supporter is formed inside the holder, wherein the protruding supporter lifts the portion between the development portion and the blood supply portion, thus forming the space. It also is preferable that a protruding holding portion is formed inside the holder on an opposite side to the side on which the protruding supporter is formed, wherein holding portion fixes the development portion to the inner wall of the holder on the side on which the protruding supporter is formed. Accordingly, the whole porous membrane also can be fixed stably.
The space is not particularly limited as long as its size prevents the capillary phenomenon from occurring and is determined suitably according to conditions such as blood viscosity (or surface tension), materials of the inner wall of the holder and the porous membrane, or the like. The space has a height of at least 0.05 mm, preferably in the range of 0.05 to 3 mm, more preferably 0.2 to 2 mm, and particularly preferably 0.3 to 0.7 mm.
In the contained-type blood testing tool, the size of the porous membrane may be determined according to the size of the inner portion of the holder. When the porous membrane has a rectangular shape, its size is, for example, in the range of 22xc3x9722 to 2xc3x97250 mm, preferably 20xc3x9725 to 3xc3x97167 mm, and more preferably 5xc3x97100 mm. The thickness of the porous membrane and the pore size are described later.
Materials for the holder may include, for example, polyethylene terephthalate (PET), polyvinyl chloride (PVC), acrylonitrile butadiene styrene copolymer (ABS), polypropylene (PP), acrylic resin, styrene, or the like. Preferably, the material of the holder is PET, ABS resin, and PP, more preferably PET and ABS resin. It also is preferable that a part of a portion of the holder corresponding to the development portion is transparent. When the part is transparent, the development of blood can be checked visually from the outside. Furthermore, the transparent portion is not limited to a part of the portion, thus the whole portion may be transparent. Examples of transparent material include acrylic resin, PET, PVC, ABS resin, or the like. Preferably, the transparent material is PET, PVC, or acrylic resin, and more preferably PET or PVC. For the same reason, a slit is preferably formed in a portion of the holder corresponding to the development portion.
In another example of a form of tool there is provided a contained-type blood testing tool further including a holder, wherein the holder contains the asymmetric porous membrane, the holder has a blood guide hole at a position corresponding to the blood supply portion, a predetermined space is provided between a lower end of the blood guide hole and the blood supply portion, and blood is retained in the space quantitatively by surface tension of the blood.
Conventionally, in a blood testing tool, quantitative analysis may be required in some cases and in such a case, it is necessary to supply a predetermined amount of blood to the blood testing tool. For instance, there is a method in which blood is collected quantitatively using a pipette or the like, which then is supplied to the blood testing tool. In another method, a blood testing tool is provided with quantitativity by the use of a capillary tube with a predetermined volume instead of an asymmetric porous membrane. In a further method, a blood testing tool is employed in which a porous membrane having quantitativity is used and blood is supplied to a particular area of the porous membrane.
However, the above method of supplying blood quantitatively using a pipette is complicated and is not practical in clinical tests requiring large amounts of blood to be treated. In the blood testing tool using the capillary tube, besides the capillary tube, an analyzor or the like is required and thus the configuration of the blood testing tool is complicated. Therefore, it is difficult to apply such a blood testing tool to multi-item tests. Such a complex configuration also makes the operation of collecting blood from the blood testing tool complicated. In addition, a porous membrane having quantitativity is expensive and therefore the use of this increases the cost of the blood testing tool. Generally, a porous membrane used in a blood testing tool is required to have various functions such as a filtration function, a function preventing effects on a reaction field, or the like. However, it is difficult to provide functions other than the quantitativity additionally for a porous membrane having quantitativity. Furthermore, a porous membrane having quantitativity tends to be affected easily by the nature of a specimen such as blood hematocrit, viscosity, or the like, therefore, it is difficult to maintain a specimen with variation in nature quantitatively. Moreover, in a conventional blood testing tool, there also is the problem that a specimen may penetrate the region between the porous membrane and the inner wall of the holder as described above, which affects the test.
According to the contained-type blood testing tool, however, the surface tension of blood may be utilized and therefore, as described above, not only can blood cells be separated adequately and an excellent collection rate be achieved, but also blood can be collected quantitatively with ease, at low cost, and with a simple configuration. In addition, since a predetermined space is provided between the lower end of the blood guide hole and the porous membrane, blood may be prevented from penetrating between the porous membrane and the inner wall of the holder. This is because no capillary phenomenon occurs due to the predetermined space in this case, since the blood penetration is caused by the capillary phenomenon.
The space has a height in the range of, for instance, 10 to 3000 xcexcm, preferably 50 to 1500 xcexcm, and more preferably 100 to 1000 xcexcm.
Preferably, the holder has a hole and an annular protrusion is formed on an inner wall of the holder so as to surround the hole, so that the blood guide hole is formed by the hole and a space inside the annular protrusion, and an end of the annular protrusion is the lower end of the blood guide hole. Such an annular protrusion serves as a guide for guiding blood to the blood supply portion of the porous membrane.
Preferably, the part of the holder corresponding to the development portion is transparent or a slit is formed in the portion as described above.
The size of the porous membrane can be determined suitably according to, for example, the size of the holder in which the porous membrane is to be contained. In the case of using a strip-shaped porous membrane, for example, it may have a length of 1 to 300 mm and a width of 1 to 100 mm, preferably a length of 5 to 100 mm and a width of 5 to 50 mm, and more preferably a length of 10 to 50 mm and a width of 5 to 20 mm. The thickness of the porous membrane and the pore size are described later.
A contained-type blood testing tool according to the present invention may have both the configurations of the above-mentioned two contained-type blood testing tools. In other words, in a third contained-type blood testing tool having such configurations, preferably, the porous membrane is contained in a holder, wherein a space with a size preventing a capillary phenomenon from occurring is formed between an inner wall of the holder and a portion between the development portion and the blood supply portion. The holder has a blood guide hole at a position corresponding to the blood supply portion of the porous membrane, a predetermined space is provided between a lower end of the blood guide hole and the blood supply portion, and blood is retained in the space quantitatively by surface tension of the blood. In this contained-type blood testing tool, details of the respective parts are the same as described above.
Preferably, in the holder used for the contained-type blood testing tool, a protruding supporter is provided inside the holder for forming a space with a size preventing the capillary phenomenon from occurring by lifting a portion between the development portion and the supply portion of the porous membrane. In addition, for the same reason as described above, preferably, a protruding holding portion is formed for fixing the porous membrane to the inner wall of the holder, in an inner portion of the holder on an opposite side to the side where the supporter is provided. Moreover, preferably, a part of the portion of the holder corresponding to the development portion of the porous membrane is transparent or a slit is formed in the portion.
The size of the holder is not particularly limited. For example, the overall size may be 5 mmxc3x9730 mm to 50 mmxc3x9780 mm, the overall thickness may be 0.5 to 10 mm, the height of the protruding supporter may be 0.05 to 3.0 mm, and the height of the protruding holding portion may be 0.1 to 5.0 mm. Preferably, the overall size is 5 mmxc3x9740 mm to 40 mmxc3x9770 mm, the overall thickness is 0.5 to 5.0 mm, the height of the protruding supporter is 0.2 to 1.0 mm, and the height of the protruding holding portion is 0.3 to 2.0 mm. More preferably, the overall size is 10 mmxc3x9750 mm to 30 mmxc3x9760 mm, the overall thickness is 1.0 to 3.0 mm, the height of the protruding supporter is 0.3 to 0.7 mm, and the height of the protruding holding portion is 0.4 to 1.0 mm.